Indole → (1-Pentyl-1H-indol-3-yl)(2,2,3,3-tetramethylcyclopropyl)methanone

HRID 1525348Notes

Reaction equation

HRID 1525348 reaction equation
[NH:1]1[C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[CH:3]=[CH:2]1.C[Mg+].[Br-].[CH3:13][C:14]1([CH3:22])[C:16]([CH3:18])([CH3:17])[CH:15]1[C:19]([OH:21])=O.[Cl-].[NH4+]>C(OCC)C.S(Cl)(Cl)=O>[CH3:2][CH2:3][CH2:4][CH2:5][CH2:6][N:1]1[C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[C:3]([C:19]([CH:15]2[C:16]([CH3:17])([CH3:18])[C:14]2([CH3:13])[CH3:22])=[O:21])=[CH:2]1

Participants

7

Reactant 4

HCID 798IndoleHCID 25517Ammonium ChlorideHCID 1521152,2,3,3-Tetramethylcyclopropanecarboxylic acidHCID 178418689HCID 178418689, compound

Product 1

HCID 44626619(1-Pentyl-1H-indol-3-yl)(2,2,3,3-tetramethylcyclopropyl)methanone

Reagents, catalysts & solvents 2

HCID 3283Diethyl EtherSolventHCID 24386Thionyl ChlorideSolvent

Conditions

Temperature
0 °C

Procedure

Indole 1 (11.7 g, 100 mmol) was dissolved in diethylether (100 ml) under nitrogen atmosphere and cooled to 0° C. 3M solution of MeMgBr (35 ml, 105 mmol) was added drop-wise and allowed to stir at room temperature for 3 hours. In the meantime, 2,2,3,3-tetramethylcyclopropane carboxylic acid (14.22 g, 100 mmol) was dissolved in thionyl chloride (100 ml) and refluxed for 90 min, then the solvent was removed under vacuo and the residue was dissolved in diethylether (100 ml). The resulting solution was added drop-wise to the indole reaction mixture at 0° C. and then allowed to stir at room temperature for 2 hours. A solution of ammonium chloride (200 ml) was added to the reaction mixture and the resulting mixture was stirred at room temperature overnight. The reaction mixture was extracted with ethyl acetate (3×200 ml). The combined organic extracts were washed by water, brine, dried over sodium sulfate, filtered and evaporated to dryness. The crude was purified by column chromatography (silica gel: 10-30% ethyl acetate in hexane) to give 8.6 g (36%) of N-desalkyl UR-144 2 as a cream solid.

Workup

  1. temperaturerefluxed for 90 min
  2. customthe solvent was removed under vacuo
  3. dissolutionthe residue was dissolved in diethylether (100 ml)
  4. additionThe resulting solution was added drop-wise
  5. customto the indole reaction mixture at 0° C.
  6. stirringto stir at room temperature for 2 hours
  7. stirringthe resulting mixture was stirred at room temperature overnight
  8. extractionThe reaction mixture was extracted with ethyl acetate (3×200 ml)
  9. washThe combined organic extracts were washed by water, brine
  10. dry with materialdried over sodium sulfate
  11. filtrationfiltered
  12. customevaporated to dryness
  13. customThe crude was purified by column chromatography (silica gel: 10-30% ethyl acetate in hexane)

Sources & evidence

ORD record
ord-194f5145267f4d6d8fa3f1fca56be96b
Source dataset
uspto-grants-2015_07
Patent number
US09079964B2

Reaction notes

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